Multivariate relative risks of type 2 diabetes according to MET-hours
for Total Physical Activity quintile, within strata of body mass index (BMI),
history of hypertension, and parental history of diabetes. Adjusted for the
same covariates as in Table 2
(BMI not included in the model). See footnotes to Table 1 for definition of metabolic equivalent task (MET).

Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification
of Diabetes Mellitus. Diabetes Care.1997;20:1183-1197.Google Scholar

Pate RR, Pratt M, Blair SN.
et al. Physical activity and public health: a recommendation from the Centers
for Disease Control and Prevention and the American College of Sports Medicine. JAMA.1995;273:402-407.Google Scholar

Context Although many studies suggest that physical activity may reduce risk
of type 2 diabetes, the role of moderate-intensity activity such as walking
is not well understood.

Objectives To examine the relationship of total physical activity and incidence
of type 2 diabetes in women and to compare the benefits of walking vs vigorous
activity as predictors of subsequent risk of type 2 diabetes.

Design and Setting The Nurses' Health Study, a prospective cohort study that included detailed
data for physical activity from women surveyed in 11 US states in 1986, with
updates in 1988 and 1992.

Participants A total of 70,102 female nurses aged 40 to 65 years who did not have
diabetes, cardiovascular disease, or cancer at baseline (1986).

Main Outcome Measure Risk of type 2 diabetes by quintile of metabolic equivalent task (MET)
score, based on time spent per week on each of 8 common physical activities,
including walking.

Results During 8 years of follow-up (534,928 person-years), we documented 1419
incident cases of type 2 diabetes. After adjusting for age, smoking, alcohol
use, history of hypertension, history of high cholesterol level, and other
covariates, the relative risks (RRs) of developing type 2 diabetes across
quintiles of physical activity (least to most) were 1.0, 0.77, 0.75, 0.62,
and 0.54 (P for trend <.001); after adjusting
for body mass index (BMI), RRs were 1.0, 0.84, 0.87, 0.77, and 0.74 (P for trend = .002). Among women who did not perform vigorous
activity, multivariate RRs of type 2 diabetes across quintiles of MET score
for walking were 1.0, 0.91, 0.73, 0.69, and 0.58 (P
for trend <.001). After adjusting for BMI, the trend remained statistically
significant (RRs were 1.0, 0.95, 0.80, 0.81, 0.74; P
for trend = .01). Faster usual walking pace was independently associated with
decreased risk. Equivalent energy expenditures from walking and vigorous activity
resulted in comparable magnitudes of risk reduction.

Strong epidemiologic evidence suggests that physical activity is associated
with reduced risk of type 2 diabetes. In cross-sectional and ecological studies,
higher levels of physical activity are associated with lower prevalence of
type 2 diabetes.1,2 Populations
who migrate to westernized countries with more sedentary lifestyles have greater
risks of type 2 diabetes than their counterparts who remain in their native
countries.2 Populations undergoing westernization
in the absence of migration, such as North American Indians3
and Western Samoans,4,5 also have
experienced increases in obesity and type 2 diabetes. Such studies must be
interpreted with caution, however. In cross-sectional studies, it is difficult
to establish cause and effect, and in the studies of migrant or westernizing
populations, many other factors in addition to physical activity undergo change,
including modifications in diet and other lifestyle factors.

More powerful support for the role of physical activity in the prevention
of type 2 diabetes has emerged in the past several years from prospective
cohort studies.6- 13
Most of these studies, however, did not examine separately the role of moderate-intensity
physical activity such as walking vs vigorous activity, although increasing
evidence supports the beneficial effects of moderate-intensity activity.14- 16 Except for subjects
in our own previous report,7 subjects in these
studies have been predominantly male. All have suggested an inverse association
between physical activity and diabetes, but there have been discrepancies
among studies in terms of the relationship between risk of type 2 diabetes
and the frequency and intensity of physical activity. Whether the effects
of physical activity on diabetes risk differ between individuals at high vs
low risk of type 2 diabetes (ie, the presence or absence of diabetes risk
factors) has also been controversial.

In this study, we used detailed and repeated assessments of physical
activity to quantify the dose-response relationship between total physical
activity and incidence of type 2 diabetes in women. We also examined in detail
the potential benefits of walking (the most common form of physical activity
in middle-aged and older populations) compared with more vigorous activity.

Methods

Subjects

The Nurses' Health Study cohort was established in 1976 when 121,700
female registered nurses aged 30 to 55 years residing in 1 of 11 US states
responded to mailed questionnaires regarding their medical history and health
practices; details have been published elsewhere.17
The subjects for the present analysis were 70,102 women from this cohort who
in 1986 were free from diagnosed diabetes, cardiovascular disease, and cancer
(except nonmelanoma skin cancer) and who completed the questions on physical
activity in 1986.

Assessment of Physical Activity

A detailed assessment of physical activity was first obtained by questionnaire
in 1986 and updated in 1988 and 1992. Subjects were asked the amount of time
they spent on average per week on each of the following physical activities:
walking; jogging; running; bicycling; calisthenics, aerobics, aerobic dance,
or rowing machine use; lap swimming; playing squash or racquetball; and playing
tennis. They were also asked about their usual walking pace, specified as
easy or casual (less than 3.2 km/h), normal, average (3.2-4.8 km/h), brisk
(4.8-6.2 km/h), and very brisk or striding (6.4 km/h or faster). From this
information, weekly energy expenditure in metabolic equivalent task–hours
(MET-hours) was calculated.18 Because only
2% of women reported a very brisk or striding pace, we combined brisk and
very brisk categories in the analyses of walking pace and diabetes risk. We
defined any physical activity requiring 6 METs or greater (a 6-fold or greater
increase above resting metabolic rate) as vigorous. These activities included
jogging, running, bicycling, performing calisthenics, lap swimming, playing
squash or racquetball, and playing tennis. In contrast, walking requires an
energy expenditure of only 2 to 4.5 METs, depending on pace, and therefore
we considered it to be a moderate-intensity activity.

The reproducibility and validity of the physical activity questionnaire
has been described elsewhere.19 In a representative
sample (n = 147) of participants in the Nurses' Health Study II cohort, the
2-year test-retest correlation for activity was 0.59. The correlation between
physical activity reported on 1-week recalls and that reported on the questionnaire
was 0.79. The correlation between activity reported in diaries and that reported
on questionnaires was 0.62. In a separate study on a population aged 20 to
59 years recruited from a university community (n = 103), the correlation
between physical activity score on a similar questionnaire and maximum oxygen
consumption was 0.54.20

Earlier analyses from this cohort had used only a single activity question
about number of episodes of vigorous (sweat-inducing) activity per week.7 These earlier analyses demonstrated an inverse association
between such vigorous activity and risk of type 2 diabetes but did not assess
the potential role of walking and other moderate-intensity activities. Walking
is by far the most prevalent physical activity among older adults21 and is feasible, accessible, and relatively safe.
We undertook the present analyses to examine the relationship between walking
and risk of type 2 diabetes.

Diagnosis of Diabetes

A supplementary questionnaire regarding symptoms, diagnostic tests,
and hypoglycemic therapy was mailed to women who indicated on any biennial
questionnaire that they had been diagnosed as having diabetes. Women reporting
a diagnosis of diabetes before 1986 were excluded from these analyses.

A case of diabetes was considered confirmed if at least 1 of the following
was reported on the supplementary questionnaire: (1) 1 or more classic symptoms
(excessive thirst, polyuria, weight loss, hunger) plus fasting plasma glucose
levels of at least 140 mg/dL (7.8 mmol/L) or random plasma glucose levels
of at least 200 mg/dL (11.1 mmol/L); (2) at least 2 elevated plasma glucose
concentrations on different occasions (fasting levels of at least 140 mg/dL
[7.8 mmol/L], random plasma glucose levels of at least 200 mg/dL [11.1 mmol/L],
and/or concentrations of at least 200 mg/dL after 2 hours or more shown by
oral glucose tolerance testing) in the absence of symptoms; or (3) treatment
with hypoglycemic medication (insulin or oral hypoglycemic agent).

All women with diabetes in these analyses were at least 40 years old
at the time of diagnosis. We excluded 27 cases of type 1 diabetes, 40 women
classified as having gestational diabetes only, and an additional 183 cases
of self-reported diabetes that did not satisfy all of our criteria for type
2 diabetes. The remaining women who reported new-onset diabetes were classified
as having type 2 diabetes and were included in the present analyses.

Because of potential associations between weight and physical activity,
no body weight criteria were used in the classification of type of diabetes
for these analyses. Our criteria for diabetes classification are consistent
with those proposed by the National Diabetes Data Group.22
The validity of this questionnaire has been verified in a subsample of this
study population.7 Among a random sample of
84 women classified by the questionnaire as having type 2 diabetes, 71 gave
permission for their medical records to be reviewed, and records were available
for 62. An endocrinologist (J.E.M.) blinded to the information reported on
the supplementary questionnaire reviewed the records according to National
Diabetes Data Group criteria.22 The diagnosis
of type 2 diabetes was confirmed in 61 (98%) of 62 of the women.7

Statistical Analysis

Person-years for each participant were calculated from the date of return
of the 1986 questionnaire to the date of confirmed type 2 diabetes, death
from any cause, or June 1, 1994, whichever came first. Incidence rates of
type 2 diabetes were obtained by dividing number of cases by person-years
in each category of physical activity. Relative risks (RRs) were computed
as the incidence rate in a specific category of MET score divided by that
in the lowest quintile, with adjustment for 5-year age categories. Tests of
linear trend across increasing categories of MET were conducted by treating
the categories as a continuous variable and assigning the median score for
the category as its value. To best represent long-term physical activity levels
of individual women and reduce measurement error, we created measures of the
cumulative average of MET scores from all available questionnaires up to the
start of each 2-year follow-up interval.23
For example, the 1986 MET score was related to the incidence of type 2 diabetes
between 1986 and 1988, and the average of the 1986 and 1988 scores was related
to the incidence between 1988 and 1990.

We used pooled logistic regression with 2-year intervals24
to adjust simultaneously for potential confounding variables including age
(5-year interval), smoking status (never; past; current smoking of 1-14, 15-24,
and 25 or more cigarettes per day), alcohol consumption (0, 1-4, 5-14, or
15 or more g/d), menopausal status and postmenopausal hormone use, parental
history of diabetes, and history of hypercholesterolemia or hypertension at
baseline. In additional analyses, we included body mass index (BMI) in quintiles
in the model to examine the degree to which the relation with physical activity
was mediated through BMI.

Results

A total of 1419 cases of type 2 diabetes were confirmed during 8 years
(534,928 person-years) of follow-up, corresponding to an incidence rate of
265 per 100,000 person-years. Table 1
shows the distributions of selected characteristics according to quintile
of total energy expenditure on physical activity, standardized to the age
distribution of the study population. Compared with their sedentary colleagues,
physically active women tended to be leaner and were less likely to be current
smokers or hypertensive. Dietary intakes of fats and cholesterol did not differ
appreciably across quintiles.

There was a progressive reduction in the age-adjusted RR of diabetes
with increasing physical activity (Table
2). After adjustment for smoking, alcohol use, history of hypertension,
and elevated cholesterol level, the RRs across quintiles of total MET-hours
per week were 1.0, 0.77, 0.75, 0.62, and 0.54 (P
for trend <.001). This inverse gradient remained statistically significant
after adjusting for BMI (RRs across quintiles were 1.0, 0.84, 0.87, 0.77,
and 0.74; P for trend = .002). Adjustment for glycemic
load, dietary fiber, and whole grain consumption did not appreciably change
the results. The physical activity score was inversely associated with risk
of type 2 diabetes in both lean and overweight women, in women with and without
a history of hypertension, and in women with and without parental history
of diabetes (Figure 1).

To minimize potential bias from subclinical disease, we conducted additional
analyses by excluding cases of type 2 diabetes that occurred during the first
2 years of follow-up (1097 cases were included in this analysis). The multivariate
RRs across quintiles of physical activity score were 1.0, 0.90, 0.83, 0.72,
and 0.61 (P for trend <.001). To address the possibility
that surveillance may have varied according to physical activity, we performed
an analysis restricted to cases reporting at least 1 symptom of diabetes at
diagnosis (n = 859 cases, 61% of all cases). Results from this subgroup were
not appreciably different from those for the entire cohort (multivariate RRs
were 1.0, 0.78, 0.79, 0.59, and 0.55; P for trend
<.001).

We examined changes in physical activity between 1986 and 1988 in relation
to the incidence of diabetes between 1988 and 1994. Compared with women who
were consistently sedentary (MET-hours per week ≤2 in both 1986 and 1988),
women who were consistently active (MET-hours per week >10.4 in both 1986
and 1988) had the lowest risk of diabetes (RR = 0.59; 95% confidence interval
[CI], 0.46-0.75). Women who increased their activity level from 2.1-10.4 MET-hours
in 1986 to >10.4 MET-hours in 1988 had a lower risk (RR = 0.71; 95% CI, 0.55-0.93)
compared with those who were consistently sedentary.

We examined the association between walking and incidence of type 2
diabetes among participants who reported no physical activity other than walking
to determine whether moderate-intensity physical activity (such as walking)
has a similar inverse association with risk of type 2 diabetes and to minimize
confounding of results by examining vigorous forms of activity. Approximately
47% of women in 1986 reported no vigorous activity, and 60% of all women reported
that they walked at least 1 hour per week. There was a strong inverse association
between walking score and risk of type 2 diabetes (Table 3). The multivariate RRs across quintiles of walking score
were 1.0, 0.91, 0.73, 0.69, and 0.58 (P for trend
<.001). Additional adjustment for BMI attenuated these RRs, but the trend
remained statistically significant (P = .01). In
addition, exclusion of women who reported they were "unable to walk" on the
1990 or 1992 questionnaire (34 cases excluded) did not alter the results.
Independent of the number of hours spent on walking, walking pace was also
significantly associated with risk of diabetes. Compared with women whose
usual walking pace was "easy, casual," multivariate RRs were 0.72 (95% CI,
0.62-0.85) for "normal, average" pace and 0.41 (95% CI, 0.33-0.52) for "brisk"
or "striding" pace (Table 4).

Approximately 6% of women reported any jogging; 3%, any running; 30%,
any biking; 12%, any swimming; 5%, playing any tennis; 27%, performing any
calisthenics, aerobics, or aerobic dance; and 0.6%, playing any squash sports.
After controlling for nonvigorous and other vigorous activities, the RRs of
type 2 diabetes across categories of time spent on calisthenics or aerobics—classified
as 0, less than 1 h/wk, and at least 1 h—were 1.0, 0.67 (95% CI, 0.55-0.81),
and 0.56 (95% CI, 0.46-0.69), respectively (P for
trend <.001). In the same model, the multivariate RRs were 0.58 (95% CI,
0.40-0.83) for jogging (any vs none), 0.74 (95% CI, 0.46-1.19) for running
(any vs none), 0.79 (95% CI, 0.57-1.10) for tennis (any vs none), 1.14 (95%
CI, 0.97-1.34) for swimming (any vs none), and 0.96 (95% CI, 0.85-1.09) for
biking (any vs none).

When included simultaneously in the same model as continuous variables,
walking and vigorous activity were associated with comparable risk reductions
for equivalent energy expenditures. The multivariate RRs associated with a
5 MET-hours per week increase in energy expenditures were 0.95 (0.92-0.98)
for vigorous activity and 0.92 (0.88-0.95) for walking.

Comment

In this large prospective cohort study, greater leisure-time physical
activity level, in terms of both duration and intensity, was associated with
reduced risk of type 2 diabetes. The dose-response relationship was consistent
in those at low or high risk for diabetes, and remained significant after
adjustment for BMI. The inverse association between energy expenditure from
walking and risk of type 2 diabetes was similar to that for total physical
activity and likewise persisted after controlling for BMI. This finding is
reassuring, since walking is a physical activity that is highly accessible,
readily adopted, and rarely associated with physical activity–related
injury. In addition, we found a strong association between walking pace and
risk of type 2 diabetes, even after adjustment for BMI and other known confounders.

Few women engaged in regular vigorous activities. Among the individual
vigorous activities, calisthenics or aerobics was associated with the greatest
reduction in type 2 diabetes risk. Other vigorous activities, including jogging,
running, and playing tennis, were also inversely associated with the risk.
Swimming and bicycling were not significantly associated with risk of diabetes.
This finding may be due to the highly variable intensity with which these
activities may be performed.

Overweight and obese people are less likely to engage in physical activity,
because excess body weight may increase the difficulty of physical activity.
This self-selection of heavy subjects for lower physical activity levels could
account in part for the attenuation of the physical activity–diabetes
relationship in regression models that included adjustment for BMI. However,
other factors may also be involved in the relationship. Physical activity
facilitates weight loss and weight maintenance.25
Therefore, individuals expending a great deal of energy on physical activity
tend to have lower adiposity. Furthermore, the adipose tissue loss resulting
from physical activity is often of visceral rather than subcutaneous fat,26- 29 and
visceral fat is strongly associated with insulin resistance and the related
metabolic syndrome. Leaner individuals have a reduced risk of diabetes.30- 32 To the extent that
physical activity causes individuals to have lower BMI, adjustment for BMI
in regression models may constitute statistical overcorrection and result
in underestimation of the true beneficial effect of physical activity.

It is biologically plausible that physical activity might reduce the
risk of type 2 diabetes, because physical activity increases glucose disposal
through a number of pathways. Physical activity has independent effects on
glucose disposal by increasing both insulin-mediated and non–insulin-mediated
glucose disposal.33 A single bout of physical
activity increases insulin-mediated glucose uptake for more than 24 hours.34 The increased insulin sensitivity occurs because
of increased number and activity of glucose transporters (especially the GLUT4
isoform), both in muscle and in adipose tissue.35,36
Glycogen synthase activity is also increased, resulting in increased glycogen
synthesis and increased nonoxidative disposal of glucose.35,36
In addition to this direct effect on glucose disposal, physical activity results
in decreased adipose tissue mass and preserved or increased lean body mass,25 which also lead to increased insulin sensitivity.
Consistent with these metabolic effects, small clinical trials have demonstrated
a benefit of physical activity in the prevention of diabetes among people
with impaired glucose tolerance.37,38

Equivalent energy expenditures from moderate or vigorous activity may
confer comparable benefits. In the Insulin Resistance Atherosclerosis Study,
both vigorous and nonvigorous activity were significantly associated with
insulin sensitivity among 1467 men and women aged 40 to 69 years.14 Daily walking combined with dietary therapy not only
reduced body weight but also improved insulin sensitivity among diabetic patients.39 Compared with structured aerobic physical activity,
moderate-intensity activity had similar benefits on cardiorespiratory fitness
and cardiovascular risk factors including blood pressure and lipid levels.15,16

Previous prospective studies have been limited but have generally found
an inverse relationship between regular physical activity and risk of type
2 diabetes.6- 11,13,40
Few studies, however, have included women or assessed the role of moderate
vs vigorous activity. Also, no previous study has provided updated assessments
of physical activity. In 4 studies,6,8,9,13
the risk of type 2 diabetes was shown to decrease with increasing amounts
of physical activity, whereas in 3 other studies,7,10,11
the degree of protection against diabetes was the same in those who exercised
the most compared with those who exercised only moderately. In all studies,
individuals whose levels of physical activity were moderate were at lower
risk of diabetes than were those who were completely sedentary. The studies
showing a dose-response relationship tended to have more detailed quantification
of the dose of physical activity, as did the present study.

Some limitations of this study deserve attention. Because our "nondiabetic"
cohort was not necessarily screened for glucose intolerance, some cases of
diabetes may have been undiagnosed. However, when the analyses were restricted
to symptomatic cases of type 2 diabetes, the findings were not appreciably
altered, suggesting that surveillance bias according to activity level is
unlikely. The diagnostic criteria for type 2 diabetes were changed in 1997,41 such that lower fasting glucose levels (>126 mg/dL
[7.0 mmol/L]) would now be considered diagnostic. We used the criteria proposed
by the National Diabetes Data Group,22 because
all our cases were diagnosed prior to June 1994. If the new criteria were
used, some women in this study classified as being without diabetes would
have been reclassified as having diabetes. However, this would not explain
our results, because inclusion of those with diabetes in the groups without
diabetes would have caused bias toward the null. In addition, our study focused
on leisure-time activity. Nonleisure energy expenditure may be also important
in the prevention of chronic diseases.42

In conclusion, this large prospective study suggests that both walking
and vigorous activity are associated with substantial reductions in risk of
type 2 diabetes in women. We observed comparable magnitudes of risk reduction
with walking and vigorous activity in this cohort, when total energy expenditures
were similar. Our findings lend additional support to current guidelines from
the Centers for Disease Control and Prevention43
and the National Institutes of Health44 that
recommend that Americans should accumulate at least 30 minutes of moderate-intensity
physical activity on most, but preferably all, days of the week.

Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification
of Diabetes Mellitus. Diabetes Care.1997;20:1183-1197.Google Scholar

Pate RR, Pratt M, Blair SN.
et al. Physical activity and public health: a recommendation from the Centers
for Disease Control and Prevention and the American College of Sports Medicine. JAMA.1995;273:402-407.Google Scholar